CD4+ T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARα to repress transcription of inflammatory cytokines, but is also essential for Th-mediated immunity, indicating complex effects of RA on Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during Th differentiation to multiple subsets. RA effects were subset-selective and were most significant in Th9 cells. RA globally antagonized Th9-promoting transcription factors and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARα. RA-RARα activity limited murine Th9-associated pulmonary inflammation, and human allergic inflammation was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARα signaling in Th differentiation, arguing for a role for RA in interleukin 9 (IL-9) related diseases.

中文翻译：

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维甲酸受体α抑制Th9转录和表观基因组程序，以减少过敏性病理。

CD4 + T辅助物（Th）的分化受到多种输入的调节，包括维生素A代谢物视黄酸（RA）。RA通过其受体RARα来抑制炎性细胞因子的转录，但对于Th介导的免疫也是必不可少的，这表明RA对Th的特异性和免疫应答的结果具有复杂的作用。我们检查了RA在Th分化为多个亚群期间对全基因组转录反应的影响。RA效应是亚组选择性的，在Th9细胞中最显着。RA全局拮抗Th9促进转录因子并抑制Th9分化。RA直接靶向扩展的Il9基因座，并通过RARα广泛修饰Th9表观基因组。RA-RARα活性限制了与鼠Th9相关的肺部炎症，人类过敏性炎症与RA靶基因表达降低有关。因此，抑制Th9程序是RA-RARα信号传导在Th分化中的主要功能，这证明了RA在白介素9（IL-9）相关疾病中的作用。